Medications for Parkinson Disease fall into three categories. The
first category includes drugs that work directly or indirectly to increase
the level of dopamine in the brain. The most common drugs for
Parkinson Disease are
dopamine precursors – substances such as levodopa that cross the blood-brain
barrier and are then changed into dopamine. Other drugs mimic dopamine or
prevent or slow its breakdown.
The second category of Parkinson
Disease drugs affects other
neurotransmitters in the body in order to ease some of the symptoms of the
disease. For example, anticholinergic drugs interfere with production
or uptake of the neurotransmitter acetylcholine. These drugs help to reduce
tremors and muscle stiffness, which can result from having more
acetylcholine than dopamine.
The third category of drugs prescribed for
includes medications that help control the non-motor symptoms of the disease,
that is, the symptoms that don't affect movement. For example, people with
Parkinson Disease-related depression may be prescribed antidepressants.
Levodopa. The cornerstone of therapy for
Parkinson Disease is the drug
levodopa (also called L-dopa). Levodopa (from the full name L-3,4-dihydroxyphenylalanine)
is a simple chemical found naturally in plants and animals. Levodopa is
the generic name used for this chemical when it is formulated for drug
use in patients. Nerve cells can use levodopa to make dopamine and
replenish the brain's dwindling supply. People cannot simply take
dopamine pills because dopamine does not easily pass through the blood-brain
barrier, a lining of cells inside blood vessels that regulates the
transport of oxygen, glucose, and other substances into the brain.
Usually, patients are given levodopa combined with another substance
called carbidopa. When added to levodopa, carbidopa delays the
conversion of levodopa into dopamine until it reaches the brain,
preventing or diminishing some of the side effects that often accompany
levodopa therapy. Carbidopa also reduces the amount of levodopa needed.
Levodopa is very successful at reducing the tremors
and other symptoms of Parkinson Disease during the early stages of the disease. It
allows the majority of people with Parkinson Disease to extend the period of time in
which they can lead relatively normal, productive lives.
Although levodopa helps most people with
Parkinson Disease, not
all symptoms respond equally to the drug. Levodopa usually helps most
with bradykinesia and rigidity. Problems with balance and other
non-motor symptoms may not be alleviated at all.
People who have taken other medications before
starting levodopa therapy may have to cut back or eliminate these drugs
in order to feel the full benefit of levodopa. People often see dramatic
improvement in their symptoms after starting levodopa therapy. However,
they may need to increase the dose gradually for maximum benefit. A high-protein
diet can interfere with the absorption of levodopa, so some physicians
recommend that patients taking the drug restrict their protein
consumption during the early parts of the day or avoid taking their
medications with protein-rich meals.
Levodopa is often so effective that some people may
temporarily forget they have Parkinson Disease during the early stages of the disease.
But levodopa is not a cure. Although it can reduce the symptoms of
it does not replace lost nerve cells and it does not stop the
progression of the disease.
Levodopa can have a variety of side effects. The
most common initial side effects include nausea, vomiting, low blood
pressure, and restlessness. The drug also can cause drowsiness or sudden
sleep onset, which can make driving and other activities dangerous.
Long-term use of levodopa sometimes causes hallucinations and
psychosis. The nausea and vomiting caused by levodopa are greatly
reduced by combining levodopa and carbidopa, which enhances the
effectiveness of a lower dose.
Dyskinesias, or involuntary movements such
as twitching, twisting, and writhing, commonly develop in people who
take large doses of levodopa over an extended period. These movements
may be either mild or severe and either very rapid or very slow. The
dose of levodopa is often reduced in order to lessen these drug-induced
movements. However, the Parkinson Disease symptoms often reappear even with lower
doses of medication. Doctors and patients must work together closely to
find a tolerable balance between the drug's benefits and side effects.
If dyskinesias are severe, surgical treatment may be considered. Because
dyskinesias tend to occur with long-term use of levodopa, doctors often
start younger Parkinson Disease patients on other dopamine-increasing drugs and switch
to levodopa only when those drugs become ineffective.
Other troubling and distressing problems may occur
with long-term levodopa use. Patients may begin to notice more
pronounced symptoms before their first dose of medication in the morning,
and they may develop muscle spasms or other problems when each dose
begins to wear off. The period of effectiveness after each dose may
begin to shorten, called the wearing-off effect. Another
potential problem is referred to as the on-off effect — sudden,
unpredictable changes in movement, from normal to parkinsonian movement
and back again. These effects probably indicate that the patient's
response to the drug is changing or that the disease is progressing.
One approach to alleviating these side effects is
to take levodopa more often and in smaller amounts. People with
should never stop taking levodopa without their physician's knowledge or
consent because rapidly withdrawing the drug can have potentially
serious side effects, such as immobility or difficulty breathing.
Fortunately, physicians have other treatment choices
for some symptoms and stages of Parkinson Disease. These therapies include the following:
Dopamine agonists. These drugs, which include bromocriptine,
pergolide, apomorphine, pramipexole, and ropinirole, mimic the role of
dopamine in the brain. They can be given alone or in conjunction with
levodopa. They may be used in the early stages of the disease, or later
on in order to lengthen the duration of response to levodopa in patients
who experience wearing off or on-off effects. They are generally less
effective than levodopa in controlling rigidity and bradykinesia. Many
of the potential side effects are similar to those associated with the
use of levodopa, including drowsiness, sudden sleep onset,
hallucinations, confusion, dyskinesias, edema (swelling due to excess
fluid in body tissues), nightmares, and vomiting. In rare cases, they
can cause compulsive behavior, such as an uncontrollable desire to
gamble, hypersexuality, or compulsive shopping. Bromocriptine and
pergolide sometimes also cause fibrosis, or a buildup of fibrous tissue,
in the heart valves or the chest cavity. Fibrosis usually goes away
once the drugs are stopped.
MAO-B inhibitors. These drugs inhibit the enzyme monoamine
oxidase B, or MAO-B, which breaks down dopamine in the brain. MAO-B
inhibitors cause dopamine to accumulate in surviving nerve cells and
reduce the symptoms of Parkinson Disease. Selegiline, also called deprenyl, is an MAO-B
inhibitor that is commonly used to treat Parkinson Disease. Studies supported by the
NINDS have shown that selegiline can delay the need for levodopa therapy
by up to a year or more. When selegiline is given with levodopa, it
appears to enhance and prolong the response to levodopa and thus may
reduce wearing-off fluctuations. Selegiline is usually well-tolerated,
although side effects may include nausea, orthostatic hypotension, or
insomnia. It should not be taken with the antidepressant fluoxetine or
the sedative mepiridine, because combining seligiline with these drugs
can be harmful. An NINDS-sponsored study of seligiline in the late
1980s suggested that it might help to slow the loss of nerve cells in
Parkinson Disease. However, follow-up studies cast doubt on this finding. Another MAO-B
inhibitor, rasagiline, was approved by the FDA in May 2006 for use in
treating Parkinson Disease.
COMT inhibitors. COMT stands for catechol-O-methyltransferase,
another enzyme that helps to break down dopamine. Two COMT inhibitors
are approved to treat Parkinson Disease in the United States: entacapone and tolcapone.
These drugs prolong the effects of levodopa by preventing the breakdown
of dopamine. COMT inhibitors can decrease the duration of "off" periods,
and they usually make it possible to reduce the person's dose of
levodopa. The most common side effect is diarrhea. The drugs may also
cause nausea, sleep disturbances, dizziness, urine discoloration,
abdominal pain, low blood pressure, or hallucinations. In a few rare
cases, tolcapone has caused severe liver disease. Because of this,
patients taking tolcapone need regular monitoring of their liver
Amantadine. An antiviral drug, amantadine, can help reduce
symptoms of Parkinson Disease and levodopa-induced dyskinesia. It is often used alone
in the early stages of the disease. It also may be used with an
anticholinergic drug or levodopa. After several months, amantadine's
effectiveness wears off in up to half of the patients taking it.
Amantadine's side effects may include insomnia, mottled skin, edema,
agitation, or hallucinations. Researchers are not certain how amantadine
works in Parkinson Disease, but it may increase the effects of dopamine.
Anticholinergics. These drugs, which include trihexyphenidyl,
benztropine, and ethopropazine, decrease the activity of the
neurotransmitter acetylcholine and help to reduce tremors and muscle
rigidity. Only about half the patients who receive anticholinergics are
helped by it, usually for a brief period and with only a 30 percent
improvement. Side effects may include dry mouth, constipation, urinary
retention, hallucinations, memory loss, blurred vision, and confusion.
When recommending a course of treatment, a doctor will
assess how much the symptoms disrupt the patient's life and then tailor
therapy to the person's particular condition. Since no two patients will
react the same way to a given drug, it may take time and patience to get the
dose just right. Even then, symptoms may not be completely alleviated.
Medications to Treat the Motor Symptoms of
Drugs that increase brain levels of
Drugs that mimic dopamine (dopamine
Drugs that inhibit dopamine breakdown (MAO-B
Drugs that inhibit dopamine breakdown (COMT
Drugs that decrease the action of
Drugs with an unknown
mechanism of action for Parkinson Disease
Medications for Non-Motor Symptoms.
Doctors may prescribe a variety of medications to treat the non-motor
symptoms of Parkinson Disease, such as depression and anxiety. For example, depression can
be treated with standard anti-depressant drugs such as amytriptyline or
fluoxetine (however, as stated earlier, fluoxetine should not be combined
with MAO-B inhibitors). Anxiety can sometimes be treated with drugs called
benzodiazepines. Orthostatic hypotension may be helped by increasing salt
intake, reducing antihypertension drugs, or prescribing medications such as
Hallucinations, delusions, and other psychotic symptoms
are often caused by the drugs prescribed for Parkinson Disease. Therefore reducing or
stopping Parkinson Disease medications may alleviate psychosis. If such measures are not
effective, doctors sometimes prescribe drugs called atypical antipsychotics,
which include clozapine and quetiapine. Clozapine also may help to control
dyskinesias. However, clozapine also can cause a serious blood disorder
called agranulocytosis, so people who take it must have their blood
National Institute of Neurological
Disorders and Stroke (NINDS)
National Institutes of Health
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